Abstract:
:Celastrol, isolated from the traditional Chinese medicinal herb Tripterygium wilfordii Hook. f. (Thunder God's Vine), has been used to treat cancer, chronic inflammatory, autoimmune and other human diseases. However, to date, the protein targets and the mechanism of action of celastrol have remained elusive. In this study, we find that celastrol can react with protein thiols in a unique covalent and reversible manner, while protein denaturing disrupts the interaction. Through a competitive chemoproteomics approach utilizing a cysteine-targeting activity-based probe, we report the proteome-wide quantitative profiling of cellular targets of celastrol in human cervical cancer HeLa cells. Representative targets are further validated via in vitro binding experiments and/or enzymatic activity assays. Bioinformatics analysis results suggest that celastrol exerts its numerous therapeutic effects through interaction with promiscuous proteins involved in various biological processes and cellular pathways.
journal_name
Mol Biosystjournal_title
Molecular bioSystemsauthors
Zhou Y,Li W,Wang M,Zhang X,Zhang H,Tong X,Xiao Ydoi
10.1039/c6mb00691dsubject
Has Abstractpub_date
2016-12-20 00:00:00pages
83-91issue
1eissn
1742-206Xissn
1742-2051journal_volume
13pub_type
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